Share This

A study led by St. Jude Children's Research Hospital scientists highlights a new approach for developing a universal influenza vaccine that could protect against multiple flu strains, including deadly pandemic strains. The research appears today in the advance online edition of the scientific journal Nature Immunology.

Related Articles

Researchers used the immune suppressing drug rapamycin to shift the immune response following flu vaccination to favor production of antibodies that broadly target flu viruses. The result was a more diverse antibody response to the vaccination that expanded protection to include pandemic strains not targeted by the vaccine. Vaccination is the most effective strategy against flu, particularly the pandemic strains that emerge periodically, but efforts to develop a single, universal vaccine against all flu strains have been unsuccessful.

The findings highlight a novel way to generate antibodies that recognize and target proteins shared by most influenza A strains rather than those unique to each strain. Antibodies are produced by B cells to recognize and defend against viruses. The same strategy might aid efforts to design vaccines against other viruses, researchers said.

Current flu vaccines emphasize production of highly specific antibodies. They target and bind tightly to strain-specific regions of hemagglutinin (HA) and neuraminidase (NA) proteins on the virus. That approach requires developing and administering a new flu vaccine each year to keep up with changes in those unique and highly variable HA and NA proteins.

Investigators showed the new strategy protected mice -- vaccinated against the H3N2 influenza A flu strain, which causes mild disease -- from succumbing to the more dangerous H5N1 and H7N9 strains weeks later. When researchers transferred antibody-rich serum from vaccinated to unvaccinated mice, the unvaccinated animals were also protected from later H5N1 infection, an indication that the protection came from antibodies rather than from other immune system components.

"This study has changed our approach to developing a universal flu vaccine," said corresponding author Maureen McGargill, Ph.D., an assistant member of the St. Jude Department of Immunology. "Instead of trying to enhance a highly specific, targeted immune response, our results show that a more diverse, less focused response provides a broader repertoire of antibodies that target different flu strains."

Influenza -- particularly pandemic strains that emerge periodically as flu viruses mix and form novel strains -- remains a global health threat. The influenza A H5N1 avian pandemic strain has a mortality rate of nearly 60 percent. The World Health Organization estimates that each year flu and flu-related complications kill more than 250,000 individuals worldwide. Vaccination is the most effective strategy to combat the infection. But existing vaccines protect against just the dominant seasonal flu strain and not emerging flu strains.

This study also advanced understanding of the role a protein named mTOR plays in generating the highly specific antibodies. Rapamycin works by inhibiting mTOR, which is involved in cell survival and proliferation. Researchers used the drug to track how blocking mTOR affected the immune response of mice following H3N2 vaccination.

Inhibiting mTOR disrupted generation of the antibodies that target specific regions of the HA proteins that are unique to each flu strain. Researchers showed that loss of mTOR delayed the formation of the immune structure called a germinal center. That is where antibodies are reshaped through a process called class switching. The process hones their focus and primes them to target flu viruses based on the unique, rather than shared, surface proteins.

The finding was surprising because previous research had highlighted a likely role for white blood cells known as CD8+ and CD4+ memory T cells for broadening the immune response against different flu strains. Unlike antibodies, the T cells recognize flu viruses based on shared internal proteins. The T cells reduce flu-related complications by eliminating flu-infected cells and speeding the virus' clearance from the body. In addition, rapamycin was known to increase the number of memory CD8+ T cells.

McGargill and her colleagues showed that memory CD8+ T cells were not required for enhanced protection in rapamycin-treated mice following vaccination and that the CD4+ cells played an indirect role. "This led us to the B-cell response and evidence that the cross-reactive antibodies provide crucial protection against different flu strains," said first author Rachael Keating, Ph.D., a St. Jude scientist.

St. Jude Children's Research Hospital. "New insight in quest for single vaccine against multiple flus." ScienceDaily. ScienceDaily, 21 October 2013. <www.sciencedaily.com/releases/2013/10/131021094121.htm>.

St. Jude Children's Research Hospital. (2013, October 21). New insight in quest for single vaccine against multiple flus. ScienceDaily. Retrieved March 31, 2015 from www.sciencedaily.com/releases/2013/10/131021094121.htm

St. Jude Children's Research Hospital. "New insight in quest for single vaccine against multiple flus." ScienceDaily. www.sciencedaily.com/releases/2013/10/131021094121.htm (accessed March 31, 2015).

Featured Research

Mar. 31, 2015  Researchers have illuminated an important distinction between mice and humans: how human livers heal. The difference centers on a protein called PPAR alpha which activates liver ... full story

Mar. 31, 2015  Researchers have recorded the first direct observations of the micro-scale mechanisms behind the ability of skin to resist tearing. The results could be applied to the improvement of artificial skin, ... full story

Mar. 31, 2015  Fewer than half of the physicians trained in the United States in 2013 received formal education or training on the subject of exercise, according to new research. "There are immense medical benefits ... full story

Mar. 31, 2015  Memory and as well as connections between brain cells were restored in mice with a model of Alzheimer's given an experimental cancer drug, researchers report. "With this treatment, cells under ... full story

Mar. 31, 2015  Increasing state alcohol taxes could prevent thousands of deaths a year from car crashes, say researchers, who found alcohol-related motor vehicle crashes decreased after taxes on beer, wine and ... full story

Mar. 31, 2015  Alcoholism takes a toll on every aspect of a person's life, including skin problems. Now, a new research report helps explain why this happens and what might be done to address it. "The clinical ... full story

Mar. 31, 2015  A new population of 'memory' immune cells has been discovered by scientists, throwing light on what the body does when it sees a microbe for the second time. This insight, and others like it, will ... full story

Mar. 31, 2015  Coronary heart disease and stroke, two of the leading causes of death in the United States, are diseases associated with heightened platelet reactivity. A new study in humans suggests an underlying ... full story

Mar. 31, 2015  A new study had researchers seeking answers to why the therapeutic benefit afforded by SSRIs was so limited in children and teenagers. If researchers can uncover the biological mechanisms preventing ... full story

Featured Videos

Solitair Device Aims to Takes Guesswork out of Sun Safety

Reuters - Innovations Video Online (Mar. 31, 2015)  The Solitair device aims to take the confusion out of how much sunlight we should expose our skin to. Small enough to be worn as a tie or hair clip, it monitors the user&apos;s sun exposure by taking into account their skin pigment, location and schedule. Matthew Stock reports.
Video provided by Reuters

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015)  Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline.
Video provided by Washington Post

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015)  Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17
Video provided by AFP

Related Stories

Mar. 13, 2015  New research findings parallel earlier results: Adding a strain of influenza B could improve effectiveness of an influenza vaccine. Findings from this study of flu vaccines delivered by a small ... full story

Aug. 15, 2012  In the quest for a universal influenza vaccine -- one that elicits broadly neutralizing antibodies that can protect against most or all strains of flu virus -- scientists have faced a sobering ... full story

Nov. 17, 2010  New research examines the limitations of currently available influenza vaccines and offers direction for developing more efficient and reliable strategies to make vaccines to protect against seasonal ... full story

Apr. 6, 2010  A researcher is tackling the problem that occurs when the influenza vaccine doesn't match the strain of the virus circulating in the community. He has found that adding a second influenza B ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.